Regulation of mRNA export, both viral and cellular, is a complex process that is only beginning to be understood, predominantly through studies of protein import/export, and viral RNA export. During the course of HSV- 1 infection, the ICP27 protein post-transcriptionally regulates viral late gene expression and is essential for viral growth. ICP27 shuttles between the nucleus and cytoplasm, and nucleocytoplasmic shuttling correlates with the cytoplasmic accumulation of viral late mRNA. Collectively, the data are consistent with a model in which ICP27 is a viral RNA export protein; however, the precise mechanism by which ICP27 regulates cytoplasmic late mRNA accumulation remains unclear. Therefore, the objective of this study is to elucidate the details of ICP27-dependent RNA export including (1) identification of particular viral RNAs bound by the ICP27 protein, (2) identification of domains within the ICP27 protein required for interactions with RNA, and (3) determination of cellular proteins that physically associate with ICP27. A comprehensive understanding of ICP27 function may lead to the development of novel antiviral therapies, and is certain to yield important insights into the fundamental aspects of nuclear transport.